This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Au nanoparticles were prepared by reduction of gold ions by citrate. The derived 12nm particles were modified with a signal peptide NLS for nuclear trafficking. Our preliminary study indicates that NLS modified nanoparticles gathered around the cancer cell nuclear membrane within 4hr after adding to the culture medium. Cell death was observed in 24hr that are associated with a significant accumulation of mRNA in the nucleus and a reduction in the cytoplasm. The signal pathway toward cell death are gradually elucidated but the structural alterations in the nuclear pore associated with such event are still unknown. This project will use cryo-EM to visualize the nuclear pore upon NLS-targeting nanoparticle treatment at different times after administration of the nanoparticles.